Cross-talk between insulin resistance and nitrogen species in hypoxia leads to deterioration of tissue and homeostasis

• Published in: International immunopharmacology Vol. 122; p. 110472
• Main Authors: Sharma, Priyanshy, Sri Swetha Victoria, V., Praneeth Kumar, P., Karmakar, Sarbani, Swetha, Mudduluru, Reddy, Amala
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2023
• Subjects: Diabetes mellitus; Glucose transport; Hypoxia; Inflammation; Insulin receptor; Nitric oxide; FFA; eNOS; MEC’s; DPP-4; CXCR(2/3/5/8); TNF; ILC2; GDM; NF-κB; ILC3; PO2; NKG2D; PI3K; RNS; VLDL; JNKs-c; VEGFR; iNOS; PAI-1; TD-MV; EOMES; IL; DSS; PKB; ARNT; Glucose transport; T-bet; PCOS; ARD; CMEC’s; Nitric oxide; ROS; Hypoxia; AMPK; mTORC1; XOX; NO; T2DM; NAFLD; MCP-1; IRS-1; NF-B; cGMP; mRNA; IRS; WAT; PHD; LPS; SOCS3; TAMs; DCs; IGF (I & II); NLRP3; VHL; Insulin receptor; OSA; GD; AGE; FADH; KM; GLP-1; HIF; HIE; SGLT2; Diabetes mellitus; VEGF; STAT3; MMPs; Inflammation; CO; NAD; TH; ETC; CD8; GLUT4; GOPD; HBOT; COPD
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.110472

During non-diabetic conditions, hypoxia induces HIF-1 and stimulates PDK1 expression, which inhibits excessive mitochondrial ROS generation by inhibiting mitochondrial respiration. In Diabetic condition, HIF-1 is inhibited by high glucose levels via a PHD-dependent mechanism. Due to the reduced PDK1 expression, there is an increase in mitochondrial respiration and an excess generation of mitochondrial ROS, which causes tissue damage. This also leads to diseases or disorders like insulin resistance, diabetic retinopathy, diabetic nephropathy, diabetic foot ulcer, cardiovascular disorder etc. Hypoxia can lead to the formation of ONOO– through the activation of iNOS and the uncoupling of eNOS. The formation of ONOO– can contribute to cellular damage and the pathophysiology of various diseases. The formation of ONOO– during hypoxia is a complex process that involves several steps. First, hypoxia can lead to the activation of iNOS and the production of NO. Second, eNOS can become uncoupled and produce superoxide, which can react with NO to form ONOO–.
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•Nitric oxide plays a very crucial part in preventing the side effects of hypoxia.•ROS and RNS are associated with areduction in IRS1 phosphorylation in tyrosine.•iNOS plays in both acute and chronic inflammatory reactions.•HIF-1 is the principal controller of oxygen homeostasis in cells.•Plant-based derivatives that can be used for the treatment of hypoxia.
Hypoxia has been linked with insulin resistance as it produces changes in the metabolism of the cell; in which the adipocytes impede the insulin receptor tyrosine, phosphorylation, directing at decreased levels of transport of glucose. At this juncture, we are focusing on cross-talk between insulin resistance and nitrogen species in hypoxia, leading to the deterioration of tissue and homeostasis. Physiological levels of nitric oxide play a very crucial role in acting as a priority effector and signaling molecule, arbitrating the body’s responses to hypoxia. Both ROS and RNS are associated with a reduction in IRS1 phosphorylation in tyrosine, which leads to reduced levels of IRS1 content and insulin response, which further leads to insulin resistance. Cellular hypoxia is a trigger to inflammatory mediators which signal tissue impairment and initiate survival requirements. But, hypoxia-mediated inflammation act as a protective role by an immune response and promotes wound healing during infection. In this review, we abridge the crosstalk between the inflammation and highlight the dysregulation in physiological consequences due to diabetes mellitus. Finally, we review various treatments available for its related physiological complications.